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Protein

Growth/differentiation factor 5

Gene

Gdf5

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Growth factor involved in bone and cartilage formation. During cartilage development regulates differentiation of chondrogenic tissue through two pathways. Firstly, positively regulates differentiation of chondrogenic tissue through its binding of high affinity with BMPR1B and of less affinity with BMPR1A, leading to induction of SMAD1-SMAD5-SMAD8 complex phosphorylation and then SMAD protein signaling transduction (By similarity). Secondly, negatively regulates chondrogenic differentiation through its interaction with NOG (By similarity). Required to prevent excessive muscle loss upon denervation. This function requires SMAD4 and is mediated by phosphorylated SMAD1/5/8 (PubMed:24076600). Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (By similarity).By similarity1 Publication

GO - Molecular functioni

GO - Biological processi

  • cell development Source: GO_Central
  • chondroblast differentiation Source: MGI
  • chondrocyte differentiation Source: MGI
  • embryonic limb morphogenesis Source: MGI
  • forelimb morphogenesis Source: MGI
  • hindlimb morphogenesis Source: MGI
  • negative regulation of chondrocyte differentiation Source: MGI
  • negative regulation of epithelial cell proliferation Source: MGI
  • negative regulation of mesenchymal cell apoptotic process Source: MGI
  • negative regulation of neuron apoptotic process Source: Ensembl
  • ossification involved in bone remodeling Source: Ensembl
  • positive regulation of BMP signaling pathway Source: MGI
  • positive regulation of chondrocyte differentiation Source: MGI
  • positive regulation of neuron differentiation Source: Ensembl
  • positive regulation of pathway-restricted SMAD protein phosphorylation Source: GO_Central
  • regulation of MAPK cascade Source: GO_Central
  • regulation of multicellular organism growth Source: MGI
  • regulation of SMAD protein signal transduction Source: Ensembl
  • response to mechanical stimulus Source: Ensembl
  • SMAD protein signal transduction Source: MGI
  • transmembrane receptor protein serine/threonine kinase signaling pathway Source: MGI

Keywordsi

Molecular functionCytokine, Growth factor
Biological processChondrogenesis

Enzyme and pathway databases

ReactomeiR-MMU-2129379 Molecules associated with elastic fibres

Names & Taxonomyi

Protein namesi
Recommended name:
Growth/differentiation factor 5
Short name:
GDF-5
Alternative name(s):
Bone morphogenetic protein 14
Short name:
BMP-14
Gene namesi
Name:Gdf5
Synonyms:Bmp14, Bp, Gdf-5
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:95688 Gdf5

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

Defects in Gdf5 are the cause of brachypodism (bp) which alters the length and numbers of bones in the limbs but spares the axial skeleton.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 27Sequence analysisAdd BLAST27
PropeptideiPRO_000003391428 – 375Sequence analysisAdd BLAST348
ChainiPRO_0000033915376 – 495Growth/differentiation factor 5Add BLAST120

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi183N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi394 ↔ 460By similarity
Disulfide bondi423 ↔ 492By similarity
Disulfide bondi427 ↔ 494By similarity
Disulfide bondi459InterchainBy similarity

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP43027
PRIDEiP43027

PTM databases

iPTMnetiP43027
PhosphoSitePlusiP43027

Expressioni

Inductioni

Induced over 300-fold in tibialis anterior muscles 3 days following denervation. High expression is maintained at least until 10 days after denervation.1 Publication

Gene expression databases

BgeeiENSMUSG00000038259
CleanExiMM_GDF5
GenevisibleiP43027 MM

Interactioni

Subunit structurei

Homodimer; disulfide-linked (By similarity). Interacts with serine proteases, HTRA1 and HTRA3 (PubMed:15206957, PubMed:14973287). Following LPS binding, may form a complex with CXCR4, HSP90AA1 and HSPA8 (By similarity). Interacts with high affinity with NOG; inhibits chondrogenesis (By similarity). Interacts with high affinity with BMPR1B and lower affinity with BMPR1A; positively regulates chondrocyte differentiation and induces SMAD-dependent signaling. Interacts with FBN1 (via N-terminal domain) and FBN2 (By similarity).By similarity2 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi199888, 2 interactors
STRINGi10090.ENSMUSP00000048079

Structurei

3D structure databases

ProteinModelPortaliP43027
SMRiP43027
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the TGF-beta family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3900 Eukaryota
ENOG410XT8Z LUCA
GeneTreeiENSGT00760000118883
HOGENOMiHOG000231514
HOVERGENiHBG107938
InParanoidiP43027
KOiK04664
OMAiLCEFPLR
OrthoDBiEOG091G09KP
TreeFamiTF316134

Family and domain databases

Gene3Di2.10.90.10, 1 hit
InterProiView protein in InterPro
IPR029034 Cystine-knot_cytokine
IPR001839 TGF-b_C
IPR001111 TGF-b_propeptide
IPR015615 TGF-beta-rel
IPR017948 TGFb_CS
PANTHERiPTHR11848 PTHR11848, 1 hit
PfamiView protein in Pfam
PF00019 TGF_beta, 1 hit
PF00688 TGFb_propeptide, 1 hit
SMARTiView protein in SMART
SM00204 TGFB, 1 hit
SUPFAMiSSF57501 SSF57501, 1 hit
PROSITEiView protein in PROSITE
PS00250 TGF_BETA_1, 1 hit
PS51362 TGF_BETA_2, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P43027-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRLPKLLTLL LWHLAWLDLE LICTVLGAPD LGQRTPGAKP GLTKAEAKER
60 70 80 90 100
PPLARNVFRP GGHIYGVGAT NARAKGSSGQ TQAKKDEPRK MPPRSGGPET
110 120 130 140 150
KPGPSSQTRQ AAARTVTPKG QLPGGKASSK AGSAPSSFLL KKTREPGTPR
160 170 180 190 200
EPKEPFRPPP ITPHEYMLSL YRTLSDADRK GGNSSVKLEA GLANTITSFI
210 220 230 240 250
DKGQDDRGPA VRKQRYVFDI SALEKDGLLG AELRILRKKP LDVAKPAVPS
260 270 280 290 300
SGRVAQLKLS SCPSGRQPAA LLDVRSVPGL DGSGWEVFDI WKLFRNFKNS
310 320 330 340 350
AQLCLELEAW ERGRAVDLRG LGFERTARQV HEKALFLVFG RTKKRDLFFN
360 370 380 390 400
EIKARSGQDD KTVYEYLFSQ RRKRRAPLAN RQGKRPSKNL KARCSRKALH
410 420 430 440 450
VNFKDMGWDD WIIAPLEYEA FHCEGLCEFP LRSHLEPTNH AVIQTLMNSM
460 470 480 490
DPESTPPTCC VPTRLSPISI LFIDSANNVV YKQYEDMVVE SCGCR
Length:495
Mass (Da):54,895
Last modified:July 27, 2011 - v2
Checksum:i8FAECD5A9C996D6E
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti98P → S2 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U08337 mRNA Translation: AAA18778.1
AL845445 Genomic DNA Translation: CAM22612.1
CH466551 Genomic DNA Translation: EDL06156.1
BC034546 mRNA Translation: AAH34546.1
CCDSiCCDS16958.1
PIRiS43294
RefSeqiNP_032135.2, NM_008109.3
UniGeneiMm.4744

Genome annotation databases

EnsembliENSMUST00000040162; ENSMUSP00000048079; ENSMUSG00000038259
GeneIDi14563
KEGGimmu:14563
UCSCiuc012chg.1 mouse

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiGDF5_MOUSE
AccessioniPrimary (citable) accession number: P43027
Secondary accession number(s): A2ARK2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: July 27, 2011
Last modified: May 23, 2018
This is version 157 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families
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